Classifications

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• • G—PHYSICS
  • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
  • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
  • G16H30/00—ICT specially adapted for the handling or processing of medical images
  • G16H30/40—ICT specially adapted for the handling or processing of medical images for processing medical images, e.g. editing
• • G—PHYSICS
  • G16—INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
  • G16H—HEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
  • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
  • G16H50/20—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
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  • G16H50/00—ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
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• • A—HUMAN NECESSITIES
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  • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
  • A61N2005/1019—Sources therefor
  • A61N2005/1024—Seeds
• • A—HUMAN NECESSITIES
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  • A61N5/1001—X-ray therapy; Gamma-ray therapy; Particle-irradiation therapy using radiation sources introduced into or applied onto the body; brachytherapy
  • A61N2005/1019—Sources therefor
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  • G06T2207/30004—Biomedical image processing
  • G06T2207/30081—Prostate

Definitions

• the invention relates to a brachytherapy treatment planning system.
• a related method and computer program product are also disclosed.
• Brachytherapy is commonly indicated for the treatment of prostate cancer. Either low dose rate, i.e. LDR, or high dose rate, i.e. HDR brachytherapy may be indicated.
• LDR brachytherapy is typically indicated for patients with low or intermediate risk prostate cancer.
• radioactive seeds are permanently implanted into the prostate to destroy nearby tumor cells.
• the patient After an initial outpatient appointment to determine the suitability of LDR brachytherapy, the patient typically undergoes an imaging procedure, for example using magnetic resonance imaging, i.e. MRI, or computed tomography, i.e. CT, to determine the exact shape and size of the prostate.
• a treatment plan that provides a desired radioactive dose distribution in the prostate is subsequently generated in accordance with this ‘treatment planning’ image.
• radioactive seeds that typically include radioactive iodine ( 125 I) are implanted under general anesthetic in predetermined positions in the prostate in accordance with the treatment plan.
• Some 20-30 needles each implant between 2 and 6 seeds, typically with the support of a mechanical grid-like device known as a template.
• One or more‘intra-treatment’ images may be made during the implantation procedure to verify the positioning of the needles and the seeds respective the anatomy. Intra-treatment images are conventionally made using X-ray, CT, or ultrasound. After the implantation, a‘post-treatment’ CT image is sometimes made in order to verify the seed implant positions and thereby confirm that the desired radioactive dose distribution will be achieved.
• the radioactivity of the LDR seeds diminishes over time, becoming negligible after around 10 months.
• HDR brachytherapy by contrast involves the temporary insertion of radioactive beads into the prostate, typically via plastic rods, i.e. catheters.
• brachytherapy is suited for both early stage and some locally-advanced prostate cancers. For example it is ideally suited to patients with high risk prostate cancer that has spread to the seminal vesicles.
• HDR brachytherapy patients typically undergo a similar initial outpatient appointment, following which an imaging procedure is used to generate a planning image and subsequently a treatment plan.
• some 15 to 20 catheters are inserted into the prostate, through each of which a radioactive bead, typically including 60 Co or 192 Ir, is inserted.
• a radioactive bead typically including 60 Co or 192 Ir
• radioactive bead is typically connected by means of a wire to an afterloader that accurately controls the bead’s position in the catheter.
• the bead is typically translated along the catheter in accordance with the therapy plan such that it remains in each of a number of
• predetermined positions i.e.‘dwell positions’
• a predetermined period i.e.‘dwell time’.
• the treatment typically takes only a few minutes, following which the catheters are withdrawn and no radioactive material remains in the prostate.
• prostate brachytherapy treatments in general including LDR and HDR brachytherapy treatments
• the prostate may change in position and size between the initial imaging procedure when the treatment planning image is generated, and the subsequent treatment-delivery phase, i.e. when the intra-treatment image(s) are generated.
• Changes in prostate position and size may for example be caused by the progression of the cancer, the swelling of the prostate, changes in the filling of the nearby bladder, or the presence of an endo-rectal, i.e. trans-rectal ultrasound‘TRUS’, probe that is typically used to generate intra-treatment ultrasound images.
• TRUS trans-rectal ultrasound
• document WO/2017/092463 discloses a system for dynamic localization of medical instruments that includes an ultrasound imaging system configured to image a volume where one or more medical instruments are deployed.
• a registration module registers two images of the one or more medical instruments to compute a transform between the two images, the two images being separated in time.
• a planning module is configured to have positions of the volume and the one or more medical instruments updated based on the transform and, in turn, update a treatment plan in accordance with the updated positions such that changes in the volume and positions of the one or more medical instruments are accounted for in the updated plan.
• the present invention seeks to improve treatment planning for brachytherapy- based prostate treatments.
• a brachytherapy treatment planning system and an associated method and computer program product are provided.
• the brachytherapy treatment planning system includes a processor configured to:
• a brachytherapy treatment plan comprising, for each of a plurality of brachytherapy seeds or catheters, a corresponding brachytherapy seed or catheter position in the planning image such that the plurality of brachytherapy seed or catheter positions in the planning image together satisfy a desired radioactive dose objective in the prostate;
• the pre-treatment image being generated later in time to the planning image and earlier in time than the insertion of any brachytherapy seed or catheter into the prostate; and to map each brachytherapy seed or catheter position in the planning image to a corresponding position in the pre-treatment image by performing a registration between the planning image and the pre-treatment image.
• various factors may affect the size, shape, and positioning of the prostate. These can include the progression of the cancer, the filling of the bladder, or the presence of a TRUS probe to generate intra-treatment images.
• the system provides that catheters that might be mis-positioned as a result of such factors become apparent to a user of the system. The user may subsequently decide to adapt part of the plan, or to generate an entirely new plan altogether.
• the pre-treatment image is generated earlier in time than the insertion of any brachytherapy seed or catheter into the prostate, the risk of such a mis-positioned brachytherapy seed or catheter intercepting an organ at risk is minimized. Treatment efficacy is thereby improved.
• the planning image and the pre-treatment image each include a corresponding organ at risk
• the processor of the system is further configured to:
• each brachytherapy seed or catheter position indicates, in the pre-treatment image, each brachytherapy seed or catheter position; and to either:
• this identification alerts the user to the consequence of delivering the current brachytherapy treatment plan.
• processor of the system is further configured to:
• a revised brachytherapy treatment plan comprising, for each of the plurality of brachytherapy seeds or catheters, a corresponding revised brachytherapy seed or catheter position in the pre-treatment image such that the plurality of revised brachytherapy seed or catheter positions in the pre-treatment image together satisfy the desired radioactive dose objective in the prostate.
• the revised brachytherapy treatment plan is made using the pre-treatment image it takes account of the up-to-date anatomy of the patient.
• each of the plurality of brachytherapy seeds or catheters includes a corresponding insertion trajectory in the planning image.
• the processor of the system is further configured to:
• this aspect provides that any catheter trajectory(ies) that might intercept an organ at risk as a result of factors such as changes in shape or position of the prostate, become apparent to a user of the system. Treatment efficacy is thereby improved. The user may subsequently decide to adapt part of the plan, or to generate an entirely new plan altogether.
• Fig. 1 illustrates an LDR brachytherapy procedure during which radioactive seeds are permanently positioned in the prostate.
• Fig. 2 illustrates an HDR brachytherapy procedure during which radioactive beads are temporarily positioned in the prostate by means of catheters.
• Fig. 3 illustrates various method steps that may be carried out in accordance with some aspects of the invention
• Fig. 4 illustrates the mapping of brachytherapy seed or catheter positions in a planning image to corresponding positions in a pre-treatment image based on a registration between the planning image and the pre-treatment image.
• Fig. 5 illustrates the mapping of brachytherapy seed or catheter insertion trajectories in a planning image to corresponding trajectories in a pre-treatment image based on the registration between the planning image and the pre-treatment image.
• a patient Prior to a brachytherapy procedure a patient typically undergoes an imaging procedure, for example MRI or computed tomography, i.e. CT, to determine the exact shape and size of the prostate.
• the planning image that results from this procedure is delineated or ‘contoured’ in order to identify the prostate and nearby critical organs. Imaging modalities such as MRI and CT are preferred for the generation of this image in view of their high resolution imaging capability.
• a treatment plan is subsequently generated from the planning image. For LDR brachytherapy this includes, for each of a number of brachytherapy seeds, a corresponding brachytherapy seed position in the planning image.
• the treatment plan includes, for each of a number of brachytherapy catheters, a corresponding brachytherapy catheter position in the planning image such that the plurality of brachytherapy catheter positions in the planning image together satisfy a desired radioactive dose objective in the prostate.
• the brachytherapy seed or catheter positions in the planning image together satisfy multiple such dose objectives.
• the dose objectives may for example include the delivery of sufficient radiation dose to the cancerous regions in the prostate, the minimization of the radiation dose to critical structure(s) such as‘organs at risk’, and the sparing of as much of the healthy nearby tissue as possible.
• Fig. 1 illustrates an LDR brachytherapy procedure during which radioactive seeds are permanently positioned in the prostate. It is however to be appreciated that the invention also finds application in other types of brachytherapy treatment planning, including the HDR brachytherapy procedure illustrated in Fig. 2.
• brachytherapy seeds are implanted into the prostate in accordance with the treatment plan.
• radioactive seeds that include radioactive iodine ( 125 I) are implanted in the patient under general anesthetic.
• Fig. 1 various parts of the male anatomy are illustrated, including prostate 11, urethra 12, bladder 13 and rectum 14. Detail of prostate 11 within the dashed circle is shown in the cutout portion.
• An ultrasound imaging probe exemplified by TRUS imaging probe 15 is typically inserted into rectum 14 in order to guide the placement of radioactive seeds 16 h into prostate 11 by catheter 17.
• Catheter 17 is typically inserted to its maximum extent and then withdrawn whilst releasing seeds 16h in their desired positions 18h. Care must be taken during the insertion of catheter 17 to avoid critical structures such as urethra 12, bladder 13, and the wall of rectum 14. To minimize this risk, TRUS imaging probe 15 is conventionally operated in a live imaging mode to generate live‘intra-treatment’ images during the implantation procedure and thereby verify the positioning of the needles and the seeds respective the anatomy. A mechanical grid-like device, template 18 is typically fixably mounted to TRUS imaging probe 15 in order to guide the release of seeds 16h by catheter 17. This ensures that the seeds are inserted in
• predetermined positions respective the live ultrasound image The depth of catheter 17 and the release of seeds 16h may be controlled manually by an operator in accordance with markings on the side of catheter 17, or instead its depth and the release of seeds 16h may be computer-controlled using a mechanical stepper device. In so doing, seeds 16h are inserted in accordance with their desired positions as defined in the planning image. It is to be noted that whilst a single catheter 17 is illustrated in Fig. 1, typically some 20-30 such catheters are used in a single procedure, each catheter implanting between 2 and 6 seeds.
• An HDR brachytherapy treatment planning phase typically shares the same initial MRI or CT imaging procedure as the above-described LDR procedure.
• the resulting treatment planning image is then used to generate an HDR brachytherapy treatment plan.
• an HDR brachytherapy treatment plan defines, for each of a number of brachytherapy catheters, a corresponding brachytherapy catheter position in the planning image such that the plurality of brachytherapy catheter positions in the planning image together satisfy a desired radioactive dose objective in the prostate.
• these HDR brachytherapy catheter positions are typically termed‘dwell positions’, the temporary radiation source, or bead, being maintained in each dwell position for a corresponding period referred-to as a‘dwell time’.
• Fig. 2 illustrates an HDR brachytherapy procedure during which radioactive beads are temporarily positioned in the prostate by means of catheters.
• Fig. 2 refers to the same item in Fig. 1.
• an ultrasound imaging probe exemplified by TRUS imaging probe 15 is typically inserted into rectum 14 in order to guide the placement of catheters 17h into prostate 11.
• Catheters 17h are typically formed from plastic, and the position of a radioactive bead within each catheter is controlled by an afterloader by means of a wire.
• the radioactive bead typically includes 60 Co or 192 Ir.
• the afterloader, wire and bead are not shown in Fig. 2.
• Each bead is translated along its catheter 17h in accordance with the therapy plan such that it remains in each position 18h defined in the planning image, i.e. each dwell position, for a predetermined time, i.e. a dwell time.
• care must be taken during the insertion of catheter 17 to avoid critical structures such as urethra 12, bladder 13, and the wall of rectum 14.
• TRUS imaging probe 15 may therefore be used in a live imaging mode to generate live‘intra- treatment’ images during the implantation procedure in order to verify the positioning of the needles and the seeds respective the anatomy.
• a template similar to template 18 may be fixably mounted to TRUS imaging probe 15 in order to guide the insertion of catheters 17h.
• Fig. 3 illustrates various method steps that may be carried out in accordance with some aspects of the invention. Whilst described in relation to FDR brachytherapy treatment planning, the method steps are also applicable to HDR brachytherapy treatment planning, and to brachytherapy treatment planning in general. In one embodiment the method described with reference to Fig. 3 may be carried out by the processor of a brachytherapy treatment planning system. Moreover, whilst illustrated as a sequential series of steps, some of these steps may be carried out in parallel or in a different order to that illustrated. The method steps disclosed herein may be recorded in the form of instructions which when executed on the processor cause the processor to carry out such method steps. The instructions may be stored on a computer program product.
• the computer program product may be provided by dedicated hardware as well as hardware capable of executing software in association with appropriate software.
• the functions can be provided by a single dedicated processor, by a single shared processor, or by a plurality of individual processors, some of which can be shared.
• explicit use of the term “processor” or“controller” should not be construed to refer exclusively to hardware capable of executing software, and can implicitly include, without limitation, digital signal processor “DSP” hardware, read only memory“ROM” for storing software, random access memory “RAM”, non-volatile storage, etc.
• embodiments of the present invention can take the form of a computer program product accessible from a computer-usable or computer-readable storage medium providing program code for use by or in connection with a computer or any instruction execution system.
• a computer-usable or computer readable storage medium can be any apparatus that may include, store, communicate, propagate, or transport the program for use by or in connection with the instruction execution system, apparatus, or device.
• the medium can be an electronic, magnetic, optical, electromagnetic, infrared, or semiconductor system, or apparatus or device, or a propagation medium. Examples of a computer-readable medium include a
• optical disks include compact disk - read only memory “CD-ROM”, compact disk - read/write“CD-R/W”, Blu-RayTM and DVD.
• the brachytherapy treatment planning system includes a processor configured to:
• brachytherapy treatment plan 41 comprising, for each of a plurality of brachytherapy seeds 16h or catheters 17h, corresponding brachytherapy seed or catheter position 18h in planning image 40 such that the plurality of brachytherapy seed or catheter positions 18n in planning image 40 together satisfy a desired radioactive dose objective in the prostate 11;
• pre-treatment image 42 corresponding to the at least a portion of a prostate 11 , pre-treatment image 42 being generated later in time to planning image 40 and earlier in time than the insertion of any brachytherapy seed or catheter into the prostate;
• Planning image 40 may for example be an MRI, a CT or an ultrasound image that includes the prostate of the patient.
• the ultrasound image may for example be generated using a TRUS probe.
• MRI and CT images are preferred in view of their relatively higher resolution than ultrasound images and therefore their improved ability to distinguish different anatomical regions.
• Pre-treatment image 42 may likewise be an MRI, a CT or an ultrasound image that includes the prostate of the patient. However, for pre-treatment image 42 an ultrasound image such as a TRUS image is preferred in view of optimizing workflow and minimizing X- ray radiation dose to the patient; sufficient anatomical detail generally being available from this relatively lower resolution imaging modality. Whereas planning image 40 is typically generated some days in advance of the delivery of the brachytherapy treatment in order to give sufficient time to generate and validate the brachytherapy treatment plan, pre-treatment image 42 is typically generated on the day of treatment, immediately prior to the insertion of any radioactive seeds or catheters into the prostate.
• radiation therapy plan 41 may be generated form the planning image in accordance with the principles disclosed in document“Recent developments and best practice in brachytherapy treatment planning”, C. D. Lee, Br. J.
• dose calculations may be computed using Monte Carlo simulations in accordance with the principles disclosed in document“Current state of the art brachytherapy treatment planning dosimetry algorithms”, Papagiannis, P, et al, Br J Radiol. September 2014; 87(1041).
• Registration 43 between planning image 40 and pre-treatment image 42 that is used in mapping 18 is preferably a rigid registration.
• contours in one or both of the images may be delineated either a manual or an automatic segmentation technique.
• a combination of manual and automatic techniques may also be used.
• Automatic segmentation automatic segmentation techniques such as model-based segmentation technique, or registering the image to an anatomical atlas that includes the at least a portion of a prostate may for example be used.
• points on the contours, or the contours themselves may be matched using a rigid registration, i.e. transformation that in a least squares sense, best matches the two images.
• a contour- based registration 43 is illustrated on the right side of Fig.
• a contour of prostate 11 from planning image 40 is overlaid on a corresponding, dashed, contour of prostate 11’ from pre-treatment image 42.
• the rigid registration process may be used in the absence of contouring, wherein points, or landmarks, on each of the two images may likewise be matched using a rigid registration, i.e. transformation that in a least squares sense, best matches the two images.
• a landmark-based registration is illustrated on the right side of Fig. 4 in which landmark 45 of prostate 11 from planning image 40 is best-matched to corresponding landmark 45’ in pre-treatment image 42.
• the above-described contouring or segmentation is performed on planning image 40, and features of the pre-treatment image including the prostate are segmented by non-rigidly registering the so-segmented planning image 40 to the pre-treatment image 42.
• This implementation may have the benefit of reducing segmentation time and/ or improving segmentation accuracy, particularly when the planning image has relatively higher resolution than the pre-treatment image.
• Registration 43 ultimately defines a vector that is used in mapping each brachytherapy seed or catheter position 18n in the planning image 40 to a corresponding position in the pre-treatment image 42.
• the position of urethra 46 is shifted upwards to position 46’ in dash-contoured pre- treatment image 42 respective solid-contoured planning image 40. This shift may for example be caused by pressure on prostate 11 following the insertion of TRUS imaging probe 15.
• the nearby brachytherapy seed position that is mapped into pre-treatment image 42 now intercepts urethra 46.
• Mapping 33 therefore serves to warn a user of the brachytherapy planning system that should the brachytherapy seeds be inserted in accordance with the current brachytherapy plan, urethra 46’ could be harmed.
• the processor may be further configured to:
• a) identify 36, in pre-treatment image 42, at least one brachytherapy seed or catheter position that intercepts organ at risk 46, or b) indicate, in the pre-treatment image 42 that no brachytherapy seed or catheter position intercepts the organ at risk 46.
• the risk of delivering the current brachytherapy treatment plan may be indicated to a user of the system.
• the identification may for example include changing the shape, color, saturation or hue of a marker corresponding to the relevant brachytherapy seed or catheter position 18h in pre-treatment image 42, highlighting said marker, causing said marker to flash intermittently, or indicating in text form the relevant intercepting position 18n.
• a user of the system may readily achieve confidence in the current brachytherapy treatment plan.
• Such identification or indication may be achieved by comparing the two or three dimensional positions of the brachytherapy seed(s) or catheter(s) respective the organ at risk.
• the indication that no brachytherapy seed or catheter position intercepts the organ at risk may for example be in the form of e.g. displayed text, or as described above, by changing the shape, color, saturation or hue of representative markers.
• the processor may be further configured to:
• a revised brachytherapy treatment plan comprising, for each of the plurality of brachytherapy seeds 16h or catheters 17h, a corresponding revised brachytherapy seed or catheter position in pre-treatment image 42 such that the plurality of revised brachytherapy seed or catheter positions in pre-treatment image 42 together satisfy the desired radioactive dose objective in the prostate 11.
• the revised brachytherapy treatment plan is made for pre-treatment image 42 it takes account of the up-to-date positions and shaped of the prostate and any organ(s) at risk. A more effective brachytherapy treatment plan may therefore be delivered.
• the revised brachytherapy treatment plan can be computed using for example the above-mentioned Monte Carlo dose simulations. In one implementation any brachytherapy seed or catheter positions that are not identified as intercepting the organ at risk are maintained in their original positions in pre-treatment image 42 and only brachytherapy seed or catheter positions that are identified as intercepting the organ at risk 46 are adjusted in the pre-treatment image.
• Brachytherapy seed or catheter positions that are identified as intercepting the organ at risk 46 may be adjusted to a new position in the pre-treatment image, or removed entirely. This implementation has the benefit of a faster re-planning time.
• the revised brachytherapy treatment plan may involve adding one or more new brachytherapy seeds or catheters to the plurality of brachytherapy seeds 16h or catheters 17h. Each new brachytherapy seed or catheter has a corresponding added brachytherapy seed or catheter position in pre-treatment image 42, such that the plurality of revised brachytherapy seed or catheter positions including the added brachytherapy seed or catheter positions in the pre-treatment image 42 together satisfy the desired radioactive dose objective in the prostate 11.
• the added positions can be used to deliver a dose that accurately meets the desired radioactive dose objective in the prostate 11.
• each of the plurality of brachytherapy seeds 16h or catheters 17h includes a corresponding insertion trajectory 47n in planning image 40.
• Fig. 5 illustrates the mapping of brachytherapy seed or catheter insertion trajectories in a planning image to corresponding trajectories in a pre-treatment image based on the registration 43 between the planning image and the pre-treatment image. Items in Fig. 5 that correspond to the same items in Fig. 4 are identified with the same labels.
• Planning image 40 and pre-treatment image 42 are illustrated as three-dimensional images in Fig. 5, although these may alternatively be two-dimensional image slices as illustrated in Fig. 4. With reference to Fig. 5, planning image 40 and pre-treatment image 42 optionally each include urethra 46, as an example of an organ at risk.
• the processor is further configured to:
• a further warning is provided to a user of the brachytherapy planning system that should the brachytherapy seeds be inserted in accordance with the brachytherapy plan, the organ at risk, in this example urethra 46, could be harmed.
• the deformation of the prostate results in an insertion trajectory that passes through the current position of the urethra.
• the processor may optionally be further configured to: display pre-treatment image 42 including organ at risk 46;
• a more robust warning is provided to the user, particularly when image slices are displayed and the interception of the organ at risk occurs in an image slice that is not currently displayed.
• a user of the system may readily achieve confidence in the current brachytherapy treatment plan. Such identification or indication may be achieved by comparing the two or three dimensional positions of the brachytherapy seed(s) or catheter(s) respective the organ at risk
• the processor may optionally be further configured to identify, in pre-treatment image 42, at least one insertion trajectory 47n that intercepts the organ at risk 46, and to:
• This step can be carried out by either adjusting the respective brachytherapy seed or catheter position 18h, or without adjusting its position, and thereby only adjusting its trajectory. The latter possibility is simpler in that no dose re-computation is required. If necessary, re-positioning of the catheter can be carried out using for example the above- mentioned Monte Carlo dose simulations.
• a brachytherapy treatment planning system has been described in which a processor of the system receives a planning image corresponding to at least a portion of a prostate; generates a brachytherapy treatment plan comprising, for each of a plurality of brachytherapy seeds or catheters, a corresponding brachytherapy seed or catheter position in the planning image such that the plurality of brachytherapy seed or catheter positions in the planning image together satisfy a desired radioactive dose objective in the prostate; receives a pre-treatment image corresponding to the at least a portion of a prostate, the pre-treatment image being generated later in time to the planning image and earlier in time than the insertion of any brachytherapy seed or catheter into the prostate; and maps each
• brachytherapy seed or catheter position in the planning image to a corresponding position in the pre-treatment image by performing a registration between the planning image and the pre-treatment image.

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